This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The most significant risk factor for neurodegeneration is aging. Strong evidence implicates protein aggregation-mediated toxicity as the cause of neurodegeneration in numerous clinically important diseases, although the mechanism(s) remains unclear. Alzheimer's disease is thought to be caused by the proteotoxicity resulting from misassembly of the secreted amyloid-beta family of peptides, the longest of which are the most aggregation prone and closely linked to pathology. In this project we strive to understand the molecular basis for protection from proteotoxicity using quantitative proteomics.